Magnussenadkins1987

Xenopus has been widely used as a model organism to study wound healing and regeneration. During early development and at tadpole stages, Xenopus is a quick healer and is able to regenerate multiple complex organs-abilities that decrease with the progression of metamorphosis. This unique capacity leads us to question which mechanisms allow and direct regeneration at stages before the beginning of metamorphosis and which ones are responsible for the loss of regenerative capacities during later stages. Xenopus is an ideal model to study regeneration and has contributed to the understanding of morphological, cellular, and molecular mechanisms involved in these processes. Nevertheless, there is still much to learn. Here we provide an overview on using Xenopus as a model organism to study regeneration and introduce protocols that can be used for studying wound healing and regeneration at multiple levels, thus enhancing our understanding of these phenomena.

The paired-domain transcription factor paired box gene 6 (PAX6) causes a wide spectrum of ocular developmental anomalies, including congenital aniridia, Peters anomaly and microphthalmia. Here, we aimed to functionally assess the involvement of seven potentially non-canonical splicing variants on missplicing of exon 6, which represents the main hotspot region for loss-of-function

variants.

By locus-specific analysis of

using Sanger and/or targeted next-generation sequencing, we screened a Spanish cohort of 106 patients with

-related diseases. Functional splicing assays were performed by in vitro minigene approaches or directly in RNA from patient-derived lymphocytes cell line, when available.

Five out seven variants, including three synonymous changes, one small exonic deletion and one non-canonical splice variant, showed anomalous splicing patterns yielding partial exon skipping and/or elongation.

We describe new spliceogenic mechanisms for

variants mediated by creating or strengthening five different cryptic donor sites at exon 6. Our work revealed that the activation of cryptic

splicing sites seems to be a recurrent and underestimated cause of aniridia. Our findings pointed out the importance of functional assessment of apparently silent

variants to uncover hidden genetic alterations and to improve variant interpretation for genetic counselling in aniridia.

We describe new spliceogenic mechanisms for PAX6 variants mediated by creating or strengthening five different cryptic donor sites at exon 6. Our work revealed that the activation of cryptic PAX6 splicing sites seems to be a recurrent and underestimated cause of aniridia. Our findings pointed out the importance of functional assessment of apparently silent PAX6 variants to uncover hidden genetic alterations and to improve variant interpretation for genetic counselling in aniridia.DICER1 syndrome is a rare paediatric autosomal dominant inherited disorder predisposing to various benign and malignant tumours. It is caused by a germline pathogenic variant in DICER1, and the second hit for tumour development is usually a missense hotspot pathogenic variant in the DICER1 ribonuclease IIIb domain. While DICER1 predisposing variants account for about 60% of ovarian Sertoli-Leydig cell tumours, no DICER1-related testicular stromal tumours have been described. learn more Here we report the first two cases of testicular stromal tumours in children carrying a DICER1 germline pathogenic variant a case of Sertoli cell tumour and a case of Leydig cell tumour diagnosed at 2 and 12 years of age, respectively. A somatic DICER1 hotspot pathogenic variant was detected in the Sertoli cell tumour. This report extends the spectrum of DICER1-related tumours to include testicular Sertoli cell tumour and potentially testicular Leydig cell tumour. Diagnosis of a testicular Sertoli cell tumour should prompt DICER1 genetic testing so that patients with a DICER1 germline pathogenic variant can benefit from established surveillance guidelines. DICER1 genetic evaluation may be considered for testicular Leydig cell tumour. Our findings suggest that miRNA dysregulation underlies the aetiology of some testicular stromal tumours.

Non-adherence to medications continues to be a burden worldwide, with significant negative consequences. Community pharmacist interventions seem to be effective at improving medication adherence. However, more evidence is needed regarding their impact on disease-specific outcomes. The aim was to evaluate the impact of a community pharmacist-led adherence management intervention on adherence and clinical outcomes in patients with hypertension, asthma and chronic obstructive pulmonary disease (COPD).

A 6-month cluster randomised controlled trial was conducted in Spanish community pharmacies. Patients suffering from hypertension, asthma and COPD were recruited. Patients in the intervention group received a medication adherence management intervention and the control group received usual care. The intervention was based on theoretical frameworks for changing patient behaviour. Medication adherence, disease-specific outcomes (Asthma Control Questionnaire (ACQ) scores, Clinical COPD Questionnaire (CCQ) scores and blood pressure levels) and disease control were evaluated. A multilevel regression model was used to analyse the data.

Ninety-eight pharmacies and 1186 patients were recruited, with 1038 patients completing the study. Patients receiving the intervention had an OR of 5.12 (95% CI 3.20 to 8.20, p<0.05) of being adherent after the 6 months. At the end of the study, patients in the intervention group had lower diastolic blood pressure levels (mean difference (MD) -2.88, 95% CI -5.33 to -0.43, p=0.02), lower CCQ scores (MD -0.50, 95% CI -0.82 to -0.18, p<0.05) and lower ACQ scores (MD -0.28, 95% CI -0.56 to 0.00, p<0.05) when compared with the control group.

A community pharmacist-led medication adherence intervention was effective at improving medication adherence and clinical outcomes in patients suffering from hypertension, asthma and COPD. Future research should explore the implementation of these interventions in routine practice.

ACTRN12618000410257.

ACTRN12618000410257.